Developing and identifying effective medications and targets for treating hepatic fibrosis is an urgent priority. Our previous research demonstrated the efficacy of artesunate (ART) in alleviating liver fibrosis by eliminating activated hepatic stellate cells (HSCs). However, the underlying mechanism remains unclear despite these findings. Notably, endocytic adaptor protein (NUMB) has significant implications for treating hepatic diseases, but current research primarily focuses on liver regeneration and hepatocellular carcinoma. The precise function of NUMB in liver fibrosis, particularly its ability to regulate HSCs, requires further investigation. This study aims to elucidate the role of NUMB in the anti-hepatic fibrosis action of ART in HSCs. We observed that the expression level of NUMB significantly decreased in activated HSCs compared to quiescent HSCs, exhibiting a negative correlation with the progression of liver fibrosis. Additionally, ART induced senescence in activated HSCs through the NUMB/P53 tumor suppressor (P53) axis. We identified NUMB as a crucial regulator of senescence in activated HSCs and as a mediator of ART in determining cell fate. This research examines the specific target of ART in eliminating activated HSCs, providing both theoretical and experimental evidence for the treatment of liver fibrosis.
Hepatic Stellate Cells/cytology* ; Liver Cirrhosis/genetics* ; Artesunate/pharmacology* ; Cellular Senescence/drug effects* ; Membrane Proteins/genetics* ; Animals ; Humans ; Nerve Tissue Proteins/genetics* ; Tumor Suppressor Protein p53/genetics* ; Male ; Mice

Objective Responding to the imperative to modernize vocational education and establish competency-oriented systems,this study investigates the development of on-campus training bases for speech and hearing rehabilitation(SHR)programs within Chinese higher vocational colleges(HVC).It analyzes their functional role and essential compo-nents,and propose a competency-oriented,modular framework for on-campus training based on World Health Organization(WHO)rehabilitation competency framework(RCF),and professional education standards.Methods This research synthesized theories of higher vocational education and practical pedagogy(e.g.,situated learn-ing,experiential learning and constructivism)with analyses of domestic and international SHR educational poli-cies and standards.It examined the strategic importance and essential components(hardware,software,human re-sources,management)of on-campus training bases in the context of higher vocational education.Synthesizing RCF with standards from ASHA(knowledge and skills acquisition,KASA),International Association of Logope-dics and Phoniatrics(IALP),and Teaching Standards for Higher Vocational Schools from Ministry of Education of the People's Republic of China,a core SHR professional competency model tailored for HVC was developed.This model subsequently guided the design of a modular on-campus training curriculum and associated pedagogi-cal approaches.Results On-campus training bases were pivotal platforms that bridge theory and practice,facilitating'teaching-learning-doing'integration within HVC SHR programs.Effective base construction necessitated synergistic integration across four key domains:hardware facilities(meeting specialized acoustic/equipment needs),software resources(case libraries,standard operating procedure and digital tools),'dual-role'human resources and robust manage-ment systems(operations,evaluation,industry-education linkages).Derived from RCF and related standards,a core SHR competency framework was developed,encompassing dimensions such as foundational knowledge and ethics,assessment(audiological;speech-language),intervention(audiological rehabilitation and technology;speech-language),and communication and collaboration.Consequently,eight core training modules were de-signed,including basic operations of hearing testing,introduction to objective hearing testing,preliminary hear-ing aid fitting,application of standardized speech-language assessment tools,simulation of articulation and voice disorder assessment and intervention,simulation of swallowing disorder screening and basic training,comprehen-sive case analysis and rehabilitation plan development,and practice of professional literacy and communication skills;detailing objectives,activities,and resources,and intended for seamless integration with theoretical cours-es and off-campus practicum,establishing a cohesive'curriculum-training-practicum'continuum.Furthermore,a suite of adaptable pedagogical models,including problem-based learning,case-based learning,simulation-based training,project-based learning and the flipped classroom,were recommended for implementing these modules.Conclusion The effective development of on-campus training bases for SHR programs in HVC necessitates establishing a systematic,competency-oriented practical teaching environment.Grounded in RCF,and essential SHR knowl-edge,skills and abilities,this study proposes a framework incorporating eight core training modules and comple-mentary pedagogical models,providing a theoretically grounded,practically applicable blueprint for enhancing the educational quality and substance of these bases within HVC.Successful realization hinges upon the synergis-tic development of the four key elements(hardware,software,human resources,management),deep integration between training activities,the curriculum,and practicum experiences,and the application of innovative pedago-gy to cultivate student potential.

OBJECTIVE To investigate the mechanism of artesunate increasing the sensitivity of hepatocellular carcinoma(HCC)cells to sorafenib in hypoxic microenvironment.METHODS Firstly,hypoxia-resistant HCC cell models were established.NAC(a ROS scavenger),necrostatin-1(a necrosis inhibitor),and ferrostatin-1(a ferroptosis inhibitor)were added to examine the effects of artesunate on the inhibition rate of HCC cells and the primary modes of cell death in hypoxic microenvironment by MTT assays.Intra-cellular levels of GSH,ROS,lipid peroxidation product MDA,and iron ions were measured using corresponding kits.Mitochondrial membrane potential changes were assessed using JC-1 staining.Western blot and qPCR were performed to detect the expression of fer-roptosis-related proteins after the addition of artesunate.RESULTS The sensitivity of HCC cells to sorafenib decreased under hy-poxic microenvironment,but artesunate significantly enhanced this sensitivity.Further analysis revealed that artesunate promoted sor-afenib-induced ferroptosis by increasing ROS levels in HCC cells(P<0.05,P<0.01,P<0.001).Additionally,artesunate was found to inhibit Nrf2 mRNA and protein levels(P<0.05,P<0.01,P<0.001)and downregulate HIF-1α expression(P<0.05,P<0.01,P<0.001).CONCLUSION Artesunate increases intracellular oxidative stress by inhibiting Nrf2 and HIF-1α protein levels,subse-quently induces ferroptosis and enhances the sensitivity of HCC cells to sorafenib in hypoxic microenvironment.

Objective To investigate the current status of breastfeeding motivation in early post-partum women and analyze the influencing factors of breastfeeding motivation.Methods A conven-ience sampling method was used to select 205 hospitalized women within 48 to 72 hours postpartum as the study subjects.The women were surveyed using a general information questionnaire,a breastfeed-ing motivation scale,a breastfeeding knowledge questionnaire,and a short-form scale for breastfeed-ing self-efficacy.Multiple linear regression analysis was conducted to explore the influencing factors of breastfeeding motivation among the women.Results The average score for autonomous motivation to-wards breastfeeding among 205 women was(49.94±7.62),and the average score for controlled mo-tivation was(23.76±3.59).The results of multiple linear regression analysis showed that age,par-ticipation in breastfeeding-related courses during pregnancy,planned duration of breastfeeding,skill dimension score of the short-form scale for breastfeeding self-efficacy,and total score on the breast-feeding knowledge questionnaire were influencing factors for the autonomous motivation score towards breastfeeding(P＜0.05);participation in breastfeeding-related courses during pregnancy,skill di-mension score on the short-form breastfeeding self-efficacy,and total score on the breastfeeding knowledge questionnaire were influencing factors for the controlled motivation score towards breast-feeding(P＜0.05).Conclusion The level of breastfeeding motivation in early postpartum women needs to be improved.Healthcare providers should focus on maternal age and planned duration of breastfeeding,strengthen breastfeeding knowledge education,and enhance maternal breastfeeding self-efficacy to improve maternal breastfeeding motivation and breastfeeding rates.

Objective:To observe the effects of transcutaneous electrical point stimulation(TEPS)on awakening,cognition,and immune function in patients undergoing laparoscopic cholecystectomy(LC)under general anesthesia.Methods:Ninety patients undergoing LC under general anesthesia were selected as the study subjects and were divided into a control group and an observation group according to the random number table method,with 45 cases in each group.The control group was operated with conventional general anesthesia.The observation group was treated with the same anesthesia as the control group,and TEPS was performed at Hegu(LI4),Zusanli(ST36),and Neiguan(PC6)before the induction of anesthesia until the completion of the operation.The quality of postoperative awakening,hemodynamic indicators,cognitive function,and immune function of patients in the two groups were compared,and the occurrence of adverse reactions was recorded.Results:The time of recovery of spontaneous breathing and extubation time of the observation group were shorter than those of the control group(P<0.05);there was no statistically significant difference in the heart rate(HR)and mean arterial pressure(MAP)between the two groups at the moment before the induction of anesthesia(T1)(P>0.05);at the moment of extubation(T2)and 5 min after extubation(T3),the HR and MAP of patients in both groups were higher than those at T1(P<0.05),and those of the observation group were lower than those of the control group(P<0.05).Preoperatively,there was no statistically significant difference in the Montreal cognitive assessment scale(MoCA)score between the two groups(P>0.05);3 d postoperatively,the MoCA score of the two groups decreased and was higher in the observation group than in the control group(P<0.05).Preoperatively,there was no statistical difference in the comparison of CD4+,CD8+,and CD4+/CD8+between the two groups(P>0.05);3 d postoperatively,the above indicators decreased in both groups(P<0.05)and were higher in the observation group than in the control group(P<0.05).There was no statistical difference in the total incidence of adverse reactions between the two groups(P>0.05).Conclusion:The application of TEPS at Hegu(LI4),Zusanli(ST36),and Neiguan(PC6)with general anesthesia can improve the quality of postoperative awakening,promote hemodynamic stabilization,and improve cognitive function and immune function in LC patients,with good safety.

To summarize the nursing management experience of 9 patients with lung transplantation undergoing extracorporeal membrane oxygenation(ECMO)combined with continuous renal replacement therapy(CRRT)during perioperative period.The key points of nursing include forming a professional team to ensure the whole process management;comprehensive evaluation and pretreatment of adverse events during the operation to maintain the safe operation of the equipment;refined volume management based on the surgical process ensures intraoperative hemodynamic stability;optimization of intraoperative anticoagulation management to reduce the incidence of complications;multi-device safe transport management ensures the continuity of postoperative treatment.Through comprehensive and targeted nursing intervention,9 patients were successfully treated with ECMO combined with CRRT during the operation.The patients were transferred out of ICU 3～12 days after the operation,and were followed up for 3 months.The patient's condition is good.

Objective:To analyze the body composition of patients diagnosed with malignant gastrointestinal tumors and to assess the impact of obesity on surgical outcomes and postoperative recovery following laparoscopic radical surgery.Methods:Patients with malignant gastrointestinal tumors who underwent laparoscopic surgery in the Department of General Surgery at the First Medical Center of the Chinese PLA General Hospital from February to October 2023 were prospectively enrolled. The body composition was measured by bioelectrical impedance analysis. Accordingly, the obese patients were selected as the obese group, while non-obese patients entered the control group using propensity score matching. The clinical data, in particular the postoperative recovery, were compared between these two groups.Results:A total of 593 patients with malignant gastrointestinal tumors were included in the analysis, including 108 patients in the obese group and 107 in the control group. The two groups significantly differed in the six minute walking test ( P=0.003), postoperative anemia ( P=0.036), white blood cell count ( P<0.001), neutrophil percent ( P<0.001), and neutrophil-to-lymphocyte ratio (NLR) ( P=0.001). The obese group exhibited a significntly higher risk of developing complications after surgery ( P=0.039). Conclusions:Obese patients with malignant gastrointestinal tumors are more likely to experience complications such as muscle weakness, anemia, infection, and inflammation after a laparoscopic radical surgery. Close monitoring and proactive perioperative interventions should be taken to mitigate such risks.

Objective To systematically analyze the characteristics of impairment of speech function and activity limitation of com-munication in children with intellectual disabilities,and to develop comprehensive rehabilitation interventions.Methods An in-depth analysis of impairments of speech functions and activity limitation of communication in children with intellectual disabilities across multiple dimensions was conducted using International Classification of Func-tioning,Disability and Health(ICF)framework,from the aspects of body structures and functions,activities and participation,and environmental factors.Integrated intervention methods were implemented within speech reha-bilitation and special education settings.Results Speech function impairments often manifested as deficits in the mental functions of language,articulation func-tions,and the fluency and rhythm of speech.Communication limitations were evident,including potential defi-cits or difficulties in speaking,listening,engaging in conversations and interpersonal interactions.Environmental factors such as family support,peer attitudes,professional services and the accessibility of assistive communica-tion technologies significantly impacted the development of speech function and communication activity in these children.This study proposed a systematic assessment methodology for children's speech function and communi-cation activity based on the ICF framework,emphasizing a holistic understanding of impairments of speech func-tions and activity limitation of communication in children with intellectual disabilities,and highlighting the im-pact of communication activity on children's learning and daily life.In speech rehabilitation therapy and educa-tional rehabilitation settings,individualized intervention strategies should be designed according to the specific characteristics of impairments of speech functions and activity limitation of communication in children with intel-lectual disabilities,focusing on fostering functional communication skills and integrating them into daily life and educational activities.Augmentative and alternative communication technologies,natural context language inter-ventions,visual supports,and peer-mediated interventions might be effective.Conclusion This study has utilized the ICF framework to systematically analyze impairments of speech functions and ac-tivity limitation of communication in children with intellectual disabilities,interms of body functions and struc-tures,activities and participation,and environmental factors.A systematic approach to promoting the develop-ment of speech function and communication activity in children with intellectual disabilities has been proposed within speech rehabilitation therapy and educational rehabilitation settings,including individualized intervention strategies,the application of assistive technologies,the use of visual support,and the implementation of peer-me-diated interventions.

A 45-year-old male patient with type 2 diabetes developed euglycemic diabetic ketoacidosis(euDKA)after combined use of ertugliflozin and metformin.Four days after medication,the patient developed chest tightness,shortness of breath,fever,accompanied by urinary frequency and dysuria.Laboratory findings showed random blood glucose of 6.5 mmol·L-1,ketone bodies of 3.1 mmol·L-1,and metabolic acidosis on arterial blood gas analysis(pH 7.27,actual bicarbonate 6.9 mmol·L-1).EuDKA was diagnosed,with suspected urinary tract infection.Ertugliflozin was promptly discontinued.Treatments such as fluid resuscitation,low-dose insulin infusion via pump,electrolyte correction,and anti-infective therapy were administred.Symptoms gradually improved,and ketone bodies turned negative after three days.Using the Naranjo's Assessment Scale,the association between euDKA and the suspected drug ertugliflozin was rated as"probable"(score 7).This case suggested that concomitant use of SGLT2 inhibitors and metformin,especially with co-existing infection,may significantly increase the risk of euDKA.Enhanced medication evaluation and monitoring were recommended in clinical practice.

Objective:To analyze and identify the risk factors for preoperative hypokalemia in patients with gastrointestinal tumors and to construct a risk prediction model.Methods:A prospective research design was implemented. Patients with gastrointestinal tumors who underwent surgical treatment at the First Medical Center of the People ′s Liberation Army General Hospital between March 2023 and February 2024 were recruited as research participants through convenience sampling. These participants were randomly allocated into a modeling group or a validation group in a 7:3 ratio. Preoperative hypokalemia was defined as the outcome indicator. Multivariate Logistic regression analysis was employed to screen for risk factors, and a nomogram was subsequently constructed and validated. Results:Finally, a total of 600 patients were included in the study. In the modeling group ( n=420), 282 were male and 138 were female, 169 patients were under 60 years old, 233 patients were aged between 60 and 80 years, and 18 patients were over 80 years old. In the verification group ( n=180), there were 123 males and 57 females. Among these, 69 patients were under 60 years old, 102 patients were aged between 60 and 80 years, and 9 patients were over 80 years old. The multivariate Logistic regression analysis revealed that body mass index, occupation type, dietary habits, 6m walking speed test, grip strength relative to body mass index, and presence of digestive tract symptoms were independent risk factors for the development of preoperative hypokalemia ( χ2 values were 8.21~27.78, all P<0.05). The results of the model validation demonstrated that the areas under the receiver operating characteristic curves for the modeling and validation groups were 0.853 (95% CI 0.811-0.895) and 0.834 (95% CI 0.756-0.912), respectively, indicating a satisfactory level of predictive performance. Conclusions:The developed predictive model for preoperative hypokalemia in gastrointestinal tumors facilitates the accurate evaluation of the risk of preoperative hypokalemia and serves as a reference for effective clinical intervention.